Complex targeting hepatitis B virus

ABSTRACT

A compound medicine for treating acute and chronic hepatitis B, includes a polyphenolic selenium compound having a functional group of alkali metal ion and selenium coordination complex, which has functions of directly killing HBV and destroying replication template of HBV. Auxiliary formulas thereof include high-purity oxymatrine and glycyrrhizin sulfate. The oxymatrine has an effect of anti-HBV, and is capable of treating acute and chronic hepatitis B, regulating immune system and increasing leukocyte. Serving as a main hepatocyte membrane protective agent, the glycyrrhizin sulfate has not only an effect of anti-inflammation, but also it is capable of regulating immune system and protecting hepatocyte. The compound medicine has no toxicity or side effect.

CROSS REFERENCE OF RELATED APPLICATION

This is a Continuation-In-Parts application of an application having anapplication number PCT/CN2013/078719, filed Jul. 3, 2013, which claimspriority under 35 U.S.C. 119(a-d) to CN 201310147738.6, filed Apr. 25,2013.

BACKGROUND OF THE PRESENT INVENTION

1. Field of Invention

The present invention relates to a medicine for treating hepatitis B,and particularly to a polyphenolic selenium compound having a functionalgroup of alkali metal ion and selenium coordination complex targetinghepatitis B virus.

2. Description of Related Arts

Hepatitis B virus (HBV) is a species of genus Orthohepadnavirus causingacute or chronic hepatitis B of human beings. The hepatitis B is adisease caused by HBV. Currently, there is no medicine capable ofcompletely curing hepatitis B. Only a few medicines are capable ofassisting patients in fighting against and inhibiting HBV to controltheir symptoms. Currently, only a small kind of medicine is capable oftargeting hepatitis B virus and the treatment effect thereof is far fromsatisfactory.

SUMMARY OF THE PRESENT INVENTION

An object of the present invention is to provide a complex capable oftargeting hepatitis B virus, comprising a principal component of alkalimetal ion and selenium coordination complex, and supplementarycomponents of glycyrrhizin sulfate and oxymatrine.

Another object of the present invention is to provide an organicselenium compound with therapeutic effects on hepatitis B.

Accordingly, in order to attain the above objects, the present inventionprovides a complex targeting hepatitis B virus, comprising apolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex which has a basic structure of anaromatic ring, wherein:

the aromatic ring comprises at least two functional groups, each ofwhich is one member selected from the group consisting of oxygenfunctional group, sulphur functional group, phosphorus functional groupand nitrogen functional group; and a selenium coordination complexfunctional group is formed by selenium, alkali metal ion and thementioned functional groups.

Beneficial effects of the present invention are described as follows.The polyphenolic selenium compound having a functional group of alkalimetal ion and selenium coordination complex of the present invention hascharacteristics of over 20% selenium content and no toxicity, and hasrevolutionary effects in killing virus, enhancing human immunity andetc.

These and other objectives, features, and advantages of the presentinvention will become apparent from the following detailed description,the attached illustrations, and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a high performance liquid chromatography diagram of a complextargeting hepatitis B virus according to a preferred embodiment of thepresent invention.

FIG. 2 is illustrations of FIG. 1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

According to a preferred embodiment of the present invention, a complextargeting hepatitis B virus comprising a principal component of apolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex, and supplementary components ofglycyrrhizin sulfate and oxymatrine,

wherein a basic structure of the polyphenolic selenium compound having afunctional group of alkali metal ion and selenium coordination complexhas an aromatic ring, wherein the aromatic ring comprises at least twofunctional groups, each of which is one member selected from the groupconsisting of oxygen functional group, sulphur functional group,phosphorus functional group and nitrogen functional group; and seleniumcoordination complex functional group is formed by selenium, alkalimetal ion and the mentioned functional groups.

According to a preferred embodiment of the present invention, apreparing method of the polyphenolic selenium compound having afunctional group of alkali metal ion and selenium coordination complexcomprises following steps of:

a) hydrolyzing lignin to obtain multiple-structural polyphenoliccompounds;

b) reacting the multiple-structural polyphenolic compounds with at leastone kind of inorganic metal base to obtain multivalent phenolic hydroxylcarboxylate; and

c) reacting the multivalent phenolic hydroxyl carboxylate with SeO₂ toobtain multivalent phenolic hydroxyl carboxylic acid seleniumcoordination complex salts, wherein the multivalent phenolic hydroxylcarboxylic acid selenium coordination complex salts are the organicselenium composition.

According to another preferred embodiment of the present invention, thecomplex targeting hepatitis B virus further comprises oxymatrine andglycyrrhizin sulfate.

Preferably, a purity of the oxymatrine≧95%, a purity of the glycyrrhizinsulfate≧98%, a mass fraction of the oxymatrine has a range of 15˜50%, amass fraction of the glycyrrhizin sulfate has a range of 10˜50%, and amass fraction of the polyphenolic selenium compound having thefunctional group of alkali metal ion and selenium coordination complexhas a range of 5˜40%.

-   -   1. The oxymatrine has direct function of anti-HBV.    -   2. The oxymatrine is capable of inhibiting activity of collagen        and preventing fibrosis of liver.    -   3. The oxymatrine is capable of blocking abnormal apoptosis of        liver cells.    -   4. The oxymatrine has a protective effect on liver failure of        experimental mice.    -   5. The oxymatrine is capable of treating chronic hepatitis.    -   6. The oxymatrine is capable of regulating the function of        immunity and increasing the amount of leukocyte in virtue of its        anti-inflammatory and antiallergenic properties.    -   7. The glycyrrhizin sulfate is capable of protecting membrane        structure of liver cells.    -   8. The glycyrrhizin sulfate has effects of anti-HBV and        preventing allergic reactions caused by the HBV.    -   9. The glycyrrhizin sulfate is capable of improving hepatic        function.

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex is illustrated, wherein the oxygenfunctional group comprises: hydroxyl, carboxylic group, phenolic group,quinonyl, quinonyl and hydroxyl, alcoholic hydroxyl, phenolic hydroxyl,sulfonic group, amino group, free quinonyl, semiquinone, quinonic oxygengroup, monomethyl, and at least one kind monomethyl-active functionalgroup which comprises methoxyl, carboxymethyl, hydroxymethyl, phenolicmethyl and methylamino group.

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex comprises the following structureof:

wherein M is alkali metal ion.

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex comprises the following structureof:

wherein R═CH₃.CH₂CH₂CH₃.

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex comprises the following structureof:

wherein R is a functional segment of alkali metal ion and seleniumcoordination complex.

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex is illustrated, wherein R has thefollowing structure of:

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex is illustrated, wherein R has thefollowing structure of:

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex is illustrated, wherein R has thefollowing structure of:

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex is illustrated, wherein R has thefollowing structure of:

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex is illustrated, wherein R has thefollowing structure of:

wherein M is alkali metal ion, X is N, S or P.

According to a preferred embodiment of the present invention, thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex is illustrated, wherein itsmolecular weight thereof is 100˜600.

According to a preferred embodiment of the present invention, aqueoussolution of the polyphenolic selenium compound having a functional groupof alkali metal ion and selenium coordination complex is weaklyalkaline, pH thereof is 7.2˜8.5, water-solubility thereof is high, andlipophilicity thereof is good.

According to a preferred embodiment of the present invention, apreparing process of the polyphenolic selenium compound having afunctional group of alkali metal ion and selenium coordination complexcomprises following steps of:

1. obtaining one kind of multiple-structural polyphenolic compound bymeans of biotechnological hydrolysis, wherein the multiple-structuralpolyphenolic compound is weakly acidic (pH: 4.5˜6.5), and has goodwater-solubility, wherein:

molecules of the multiple-structural polyphenolic compound have aromaticrings or other heterocycles such aspyrrole, furan, indole and etc.; thearomatic rings are connected by bridge bond; the aromatic rings may havea variety of active functional groups comprising: hydroxyl, carboxylicgroup, phenolic group, phenolic hydroxyl, quinonyl, quinonyl andhydroxyl, alcoholic hydroxyl, sulfonic group, amino group, freequinonyl, semiquinone, quinonic oxygen group, monomethyl, and at leastone kind monomethyl-active functional group which comprises methoxyl,carboxymethyl, hydroxymethyl, phenolic methyl and methylamino group;

2. reacting the multiple-structural polyphenolic compound with at leastone kind of inorganic alkali metal to obtain low-aromaticity multivalentphenolic hydroxyl carboxylate, which is polymeric, nonhomogeneous,alkaline (pH: 10˜12), has high solubility and is capable of dissolvinginto multiple solvents;

3. reacting the multivalent phenolic hydroxyl carboxylate with SeO₂ toobtain low-aromaticity multivalent phenolic hydroxyl carboxylic acidselenium coordination complex salts, wherein a functional group thereofis alkali metal ion and selenium coordination complex, aqueous solutionthereof is weakly alkaline (pH: 7.2˜8.0), water solubility thereof ishigh, and lipophilicity thereof is good;

wherein the multivalent phenolic hydroxyl carboxylic acid seleniumcoordination complex salts consist of a plurality of polyphenolicstructures with functional fragments of alkali metal ion and seleniumcoordination complex.

Fundamental structure of the polyphenolic selenium compound having afunctional group of alkali metal ion and selenium coordination complexis bigeminal or poly-phenolic hydroxyl, methoxyl, carboxylic group,quinonyl and hydroxyl and etc.

The polyphenolic selenium compound having the functional group of alkalimetal ion and selenium coordination complex is newly produced compound.

Principle of the present invention is as follows. Taking advantage ofisosteric principle, N, S or P in functional groups of themultiple-structural polyphenolic compounds is replaced by Se, or N, S orP in the functional groups of the multiple-structural polyphenoliccompounds is connected with Se by covalent bond to form the alkali metalion and selenium coordination complex.

The alkali metal ion forms bidentate or multidentate coordinate bondwith O, S, N or P, and O also forms bidentate or multidentate coordinatebond with Se.

Example 1

A polyphenolic selenium compound having a functional group of alkalimetal ion and selenium coordination complex has the following structureof:

wherein M is alkali metal ion.

In this example, the structure

is capable of serving as a functional group

R in other structures.

In this example, a preparing process of the polyphenolic seleniumcompound having the functional group of alkali metal ion and seleniumcoordination complex comprises following steps of:

a) adding 2.0% urea into lignosulfonate-water solution containing 20%solid formation for serving as growth medium (pH=6.0), wherein thelignosulfonate-water solution is extracted from depickling paper pulp bysulphuric acid; inoculating the growth medium with 2% mixed strainscomprising: candida tropicalis, pseudomonas, candida utilis and strainsof effective microorganisms from Japan, and fermenting for 72 hoursunder a temperature of 30° C. to obtain the multiple-structuralpolyphenolic compounds, wherein an inoculation proportion thereof is1:2:2:2; and

b) reacting the multiple-structural polyphenolic compounds with sodiumhydroxide to obtain multivalent phenolic hydroxyl sodium carboxylate,wherein multiple-structural polyphenolic compounds:sodiumhydroxide=1:1˜0.1, wherein a reaction temperature thereof is 120° C.,and materials are mechanically stirred to be uniformly mixed whilereacting; and

c) reacting the multivalent phenolic hydroxyl sodium carboxylate withSeO₂ to obtain multivalent phenolic hydroxyl carboxylic acid seleniumcoordination complex salts, wherein the multivalent phenolic hydroxylcarboxylic acid selenium coordination complex salts are organic seleniumcomposition, multivalent phenolic hydroxyl sodium carboxylate:SeO₂=1:1˜0.1, a reaction temperature thereof is 150° C., and materialsare mechanically stirred to be uniformly mixed while reacting.

Moreover, other various structures of compounds of the present inventionare also obtained by means of the above mentioned preparing process ofthe polyphenolic selenium compound having the functional group of alkalimetal ion and selenium coordination complex.

The above produced polyphenolic selenium compound having a functionalgroup of alkali metal ion and selenium coordination complex is mixedwith oxymatrine and glycyrrhizin sulfate and then dried, in such amanner that the complex targeting hepatitis B virus of the presentinvention is obtained.

Example 2

A polyphenolic selenium compound having a functional group of alkalimetal ion and selenium coordination complex has the following structureof:

wherein R═CH₃.CH₂CH₂CH₃.

In this example, a preparing process of the polyphenolic seleniumcompound having the functional group of alkali metal ion and seleniumcoordination complex comprises following steps of:

a) adding 2.0% urea into lignosulfonate-water solution containing 20%solid formation for serving as growth medium (pH=6.0), wherein thelignosulfonate-water solution are extracted from depickling paper pulpby sulphuric acid; inoculating the growth medium with 2% mixed strainscomprising: candida tropicalis, pseudomonas, candida utilis and strainsof effective microorganisms from Japan, and fermenting for 72 hoursunder a temperature of 30° C. to obtain the multiple-structuralpolyphenolic compounds, wherein an inoculation proportion thereof is1:2:2:2; and

b) reacting the multiple-structural polyphenolic compounds withpotassium hydroxide to obtain multivalent phenolic hydroxyl potassiumcarboxylate, wherein multiple-structural polyphenoliccompounds:potassium hydroxide=1:1˜0.1, wherein a reaction temperaturethereof is 120° C., and materials are mechanically stirred to beuniformly mixed while reacting; and

c) reacting the multivalent phenolic hydroxyl potassium carboxylate withSeO₂ to obtain multivalent phenolic hydroxyl carboxylic acid seleniumcoordination complex salts, wherein the multivalent phenolic hydroxylcarboxylic acid selenium coordination complex salts are organic seleniumcomposition, multivalent phenolic hydroxyl potassium carboxylate:SeO₂=1:1˜0.1, a reaction temperature thereof is 140° C., and materialsare mechanically stirred to be uniformly mixed while reacting.

Moreover, other various structures of compounds of the present inventionare also obtained by means of the above mentioned preparing process ofthe polyphenolic selenium compound having the functional group of alkalimetal ion and selenium coordination complex.

The above produced polyphenolic selenium compound having a functionalgroup of alkali metal ion and selenium coordination complex is mixedwith oxymatrine and glycyrrhizin sulfate and then dried, in such amanner that the complex targeting hepatitis B virus of the presentinvention is obtained.

Example 3

A polyphenolic selenium compound having a functional group of alkalimetal ion and selenium coordination complex has the following structureof:

wherein R is a functional fragment of alkali metal ion and seleniumcoordination complex.

In this example, a preparing process of the polyphenolic seleniumcompound having the functional group of alkali metal ion and seleniumcoordination complex comprises following steps of:

a) adding 2.0% urea into lignosulfonate-water solution containing 20%solid formation for serving as growth medium (pH=6.0), wherein thelignosulfonate-water solution are extracted from depickling paper pulpby sulphuric acid; inoculating the growth medium with 2% mixed strainscomprising: candida tropicalis, pseudomonas, candida utilis and strainsof effective microorganisms from Japan, and fermenting for 72 hoursunder a temperature of 30° C. to obtain the multiple-structuralpolyphenolic compounds, wherein an inoculation proportion thereof is1:2:2:2; and

b) reacting the multiple-structural polyphenolic compounds with at leastone kind of inorganic metal base such as NaOH or KOH to obtainmultivalent phenolic hydroxyl sodium carboxylate or multivalent phenolichydroxyl potassium carboxylate, etc.; and

c) reacting the multivalent phenolic hydroxyl sodium/potassiumcarboxylate and etc. with SeO₂ to obtain multivalent phenolic hydroxylcarboxylic acid selenium coordination complex salts comprising Na or Kor other alkali metal, wherein the multivalent phenolic hydroxylcarboxylic acid selenium coordination complex salts are organic seleniumcomposition, multivalent phenolic hydroxyl carboxylic acid seleniumcoordination complex salts comprising alkali metal: SeO₂=1:1˜0.1, areaction temperature thereof is 140° C., and materials are mechanicallystirred to be uniformly mixed while reacting.

Moreover, other various structures of compounds of the present inventionare also obtained by means of the above mentioned preparing process ofthe polyphenolic selenium compound having the functional group of alkalimetal ion and selenium coordination complex.

The above produced polyphenolic selenium compound having a functionalgroup of alkali metal ion and selenium coordination complex is mixedwith oxymatrine and glycyrrhizin sulfate and then dried, in such amanner that the complex targeting hepatitis B virus of the presentinvention is obtained.

After taking the complex targeting hepatitis B virus obtained accordingto a preferred embodiment of the present invention, following volunteersall achieve effective therapeutic results.

Therapeutic Effects of the Medicine on Volunteers Volunteer 1 Sex: maleAge: 62

The volunteer takes 0.4 g solid capsule of the complex targetinghepatitis B virus twice daily, morning and evening, wherein thepolyphenolic selenium compound having the functional group of alkalimetal ion and selenium coordination complex is prepared according to thepreferred embodiment 1 of the present invention, a purity of theoxymatrine is 95%, a mass fraction of the oxymatrine is 40%, a purity ofthe glycyrrhizin sulfate is 98%, a mass fraction of the glycyrrhizinsulfate is 40%, and a mass fraction of the polyphenolic seleniumcompound having the functional group of alkali metal ion and seleniumcoordination complex is 20%.

Medical Examination Result Prior to the Medicine Administration May 11,2012 Code of item Name of item Result Reference value Unit HBV-DNA DNAof HBV 4.48E+06 <1.0*10{circumflex over ( )}3 copies/ml

Medical Examination Result Posterior to the Medicine Administration Sep.10, 2012 Minimum detection Code of item Name of item Result Unit limitHBV-DNA DNA of HBV Less than minimum IU/ml 5.00E{circumflex over ( )}2detection limitMedical Diagnostics Prior to the Medicine Administration

The maximum value of fasting blood glucose is 19.3, and the value of2-hour postprandial blood glucose reaches 35.4. The volunteer carrieshepatitis B virus.

Symptoms prior to the medicine administration: myasthenia of limbs, drymouth, thirsty, frequent micturition, hunger, sweating due to debility,marasmus and insomnia. After therapy with insulin at hospital, the bloodglucose has become normal. The volunteer takes entecavir for treatinghepatitis.

Self-description by the volunteer is as follows. Appetite, defecation,sleep, stamina and emotion are all in normal condition. The volunteer 1feels good, his limbs are powerful, his motion is normal. The volunteer1 plays ping-pong every day. The past abnormal symptoms disappear, noabnormal feelings now.

Onset time of curative effect: 20 days posterior to the medicineadministration, it took effect. After continuous administration of themedicine for 50 days, the patient is cured.

Medical Examination Result Posterior to Drug Withdrawal for 3 MonthsDec. 24, 2012 Minimum detection Code of item Name of item Result Unitlimit HBV-DNA DNA of HBV Less than minimum IU/ml 5.00E{circumflex over( )}2 detection limit Volunteer 2 Sex: male Age: 41 Medical record:hepatitis B cirrhosis

The volunteer takes 0.4 g solid capsule of the complex targetinghepatitis B virus twice daily, morning and evening, wherein thepolyphenolic selenium compound having the functional group of alkalimetal ion and selenium coordination complex is prepared according to thepreferred embodiment 1 of the present invention, a purity of theoxymatrine is 95%, a mass fraction of the oxymatrine is 40%, a purity ofthe glycyrrhizin sulfate is 98%, a mass fraction of the glycyrrhizinsulfate is 40%, and a mass fraction of the polyphenolic seleniumcompound having the functional group of alkali metal ion and seleniumcoordination complex is 20%.

Medical Examination Result Prior to the Medicine Administration Jan. 11,2013 Item for Reference Item name short Result Unit value Hepatitis Bvirus DNA HBV- 9.36 × 10{circumflex over ( )}2 IU/ml <40 quantity DNATotal protein TP 83    g/L 60~83 Albumin ALB 46    g/L 35~55 GlobulinGLO 36    g/L Ratio of albumin to globulin A/G 1.28 Prealbumin PAL142↓   mg/L 160~400 Direct bilirubin DBIL 19.2↑ umol/L  0~6.8 Totalbilirubin TBIL 41.7↑ umol/L  3.4~20.5 Ratio of direct to total D/T 0.46bilirubin Alanine aminotransferase ALT 404↑   U/L  5~40 Aspartateaminotransferase AST 270↑   U/L  8~40 Ratio of AST/ALT S/T 0.67 Alkalinephosphatase ALP 138    U/L  40~150 R-glutamyl transpeptidase GGT 88↑  U/L 11~50 Total bile acid TBA 26↑   umol/L  0~10 Cholinesterase CHE5998     U/L  5400~13200 Lactate dehydrogenase LDH 221    U/L 109~2455′-ribonuclease 5NT 6   U/L  0~10 Adenosine deaminase ADA 51↑   U/L 0~20 Urea UREA 4.6  mmol/L 2.9~8.2 Creatinine CRE 87    umol/L  62~115Uric acid UA 317    umol/L 208~428 Alpha-fetoprotein AFP 14    ng/ml 0~20 Leukocyte WBC 5.01 10{circumflex over ( )}9/L  4~10 Leutrophilspercentage NE %  0.637 0.5~0.7 Absolute neutrophil count NE# 3.2 10{circumflex over ( )}9/L 2~7 Lymphocyte percentage LY %  0.201 0.2~0.4Absolute lymphocyte count LY# 1.01 10{circumflex over ( )}9/L 0.8~4.0Monocytes percentage M0 %  0.087 0.03~0.1  Absolute monocytes count M0#0.43 10{circumflex over ( )}9/L 0.12~1.0  Eosinophils percentage E0 %  0.069↑ 0.005~0.05  Absolute eosinophils count E0 0.35 10{circumflexover ( )}9/L 0.02~0.5  Basophil percentage BA %  0.006   0~0.01 Absolutebasophil count BA# 0.03 10{circumflex over ( )}9/L  0~0.1 ErythrocyteRBC 4.95 10{circumflex over ( )}12/L  4~5.5 Hemoglobin HGB 161.00  g/L131~172 Hematocrit HCT 48.10  %  38~50.8 Mean corpuscular volume 97.2 fL 82.6~99.1 Corpuscular hemoglobin 336    g/L 320~362 concentrationMean corpuscular 32.6  pg 26.9~33.8 hemoglobin Erythrocyte hemoglobin14.6  %  0~15 distribution width Platelet PLT 102.00  10{circumflex over( )}9/L 100~300 Thrombocytocrit  0.099 0.06~0.40 Mean platelet volume9.7  fL 7.54~11.2 Platelet distribution width PDW 11.2  %  9.0~18.0Platelet large cell ratio P-LCR 24.5  % 13~43

Medical Examination Result Posterior to the Medicine Administration forOne Month Testing method: fluorescent quantitative nucleic acid testingTesting time: Feb. 8, 2013 Reference Name of item Item Result Unit valueFluorescent quantitative HBV- 1.14 × 10{circumflex over ( )}2 IU/ml <40nucleic acid testing HBV DNA Item for Reference Item name short ResultUnit value Total protein TP 76    g/L 60~83 Albumin ALB 45    g/L 35~55Globulin GLO 32    g/L Ratio of albumin to globulin A/G 1.42 prealbuminPAL 159↓   mg/L 160~400 Direct bilirubin DBIL  9.6↑ umol/L   0~6.8 Totalbilirubin TBIL 20.1↑ umol/L  3.4~20.5 Ratio of direct to total D/T 0.48bilirubin Alanine aminotransferase ALT 58↑   U/L  5~40 Aspartateaminotransferase AST 44↑   U/L  8~40 Ratio of AST/ALT S/T 0.80 Alkalinephosphatase ALP 114    U/L  40~150 r-glutamyl transpeptidase GGT 44↑  U/L 11~50 Total bile acid TBA 30↑   umol/L  0~10 Cholinesterase CHE6752     U/L  5400~13200 Lactate dehydrogenase LDH 157    U/L 109~2455′-ribonuclease 5NT 3   U/L  0~10 Adenosine deaminase ADA 37↑   U/L 0~20 Urea UREA 3.6  mmol/L 2.9~8.2 Creatinine CRE 91    umol/L  62~115Uric acid UA 360    umol/L 208~428 Leukocyte WBC 4.85 10{circumflex over( )}9/L  4~10 Leutrophils percentage NE %  0.611 0.5~0.7 Absoluteneutrophil count NE# 3.0  10{circumflex over ( )}9/L 2~7 Lymphocytepercentage LY %  0.244 0.2~0.4 Absolute Lymphocyte count LY# 1.1810{circumflex over ( )}9/L 0.8~4.0 Monocytes percentage M0 %  0.0910.03~0.1  Absolute monocytes count M0# 0.45 10{circumflex over ( )}9/L0.12~1.0  Eosinophils percentage E0 %  0.050 0.005~0.05  Absoluteeosinophils count E0 0.24 10{circumflex over ( )}9/L 0.02~0.5  Basophilpercentage BA %  0.004   0~0.01 Absolute basophil count BA# 0.0210{circumflex over ( )}9/L   0~0.1 Erythrocyte RBC 4.89 10{circumflexover ( )}12/L   4~5.5 Hemoglobin HGB 160.00  g/L 131~172 Hematocrit HCT47.20  %   38~50.8 Mean corpuscular volume 96.6  fL 82.6~99.1Corpuscular hemoglobin 339    g/L 320~362 concentration Mean corpuscular32.8  pg 26.9~33.8 hemoglobin Erythrocyte hemoglobin 14.3  %  0~15distribution width Platelet PLT  94.00↓ 10{circumflex over ( )}9/L100~300 Thrombocytocrit  0.088 0.06~0.40 Mean platelet volume 9.3  fL7.54~11.2 Platelet distribution width PDW 11.0  %  9.0~18.0 Plateletlarge cell ratio P-LCR 21.5  % 13~43

Onset time of curative effect: after a continuous medicineadministration for one month, copies of HBV decreased by nearly 90%.

One skilled in the art will understand that the embodiment of thepresent invention as shown in the illustrations and described above isexemplary only and not intended to be limited.

It will thus be seen that the objects of the present invention have beenfully and effectively accomplished. Its embodiments have been shown anddescribed for the purposes of illustrating the functional and structuralprinciples of the present invention and are subject to change withoutdeparture from such principles. Therefore, this invention includes allmodifications encompassed within the spirit and scope of the followingclaims.

What is claimed is:
 1. A complex targeting hepatitis B virus, comprisinga polyphenolic selenium compound having a functional group of alkalimetal ion and selenium coordination complex which has an aromatic ring,wherein: the aromatic ring comprises at least two functional groups,each functional group is one member selected from the group consistingof oxygen functional group, sulphur functional group, phosphorusfunctional group and nitrogen functional group, and seleniumcoordination complex functional group formed by selenium, alkali metalion and the oxygen functional group, the sulphur functional group, thephosphorus functional group or the nitrogen functional group.
 2. Thecomplex targeting hepatitis B virus, as recited in claim 1, furthercomprising oxymatrine and glycyrrhizin sulfate.
 3. The complex targetinghepatitis B virus, as recited in claim 2, wherein a purity of theoxymatrine≧95%, a purity of the glycyrrhizin sulfate≧98%, a massfraction of the oxymatrine has a range of 15˜50%, a mass fraction of theglycyrrhizin sulfate has a range of 10˜50%, and a mass fraction of thepolyphenolic selenium compound having the functional group of alkalimetal ion and selenium coordination complex has a range of 5˜40%.
 4. Thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex, as recited in claim 1, whereinthe oxygen functional group comprises: hydroxyl, carboxylic group,phenolic group, quinonyl, quinonyl and hydroxyl, alcoholic hydroxyl,phenolic hydroxyl, sulfonic group, amino group, free quinonyl,semiquinone, quinonic oxygen group, monomethyl, and at least one kindmonomethyl-active functional group which comprises methoxyl,carboxymethyl, hydroxymethyl, phenolic methyl and methylamino group. 5.The polyphenolic selenium compound having a functional group of alkalimetal ion and selenium coordination complex, as recited in claim 1,wherein a structure thereof comprises

wherein M is alkali metal ion.
 6. The polyphenolic selenium compoundhaving a functional group of alkali metal ion and selenium coordinationcomplex, as recited in claim 1, wherein a structure thereof comprises:

wherein R═CH₃.CH₂CH₂CH₃.
 7. The polyphenolic selenium compound having afunctional group of alkali metal ion and selenium coordination complex,as recited in claim 1, wherein a structure thereof comprises:

wherein R is alkali metal ion and selenium coordination complex.
 8. Thepolyphenolic selenium compound having a functional group of alkali metalion and selenium coordination complex, as recited in claim 7, wherein Rhas following structure of


9. The polyphenolic selenium compound having a functional group ofalkali metal ion and selenium coordination complex, as recited in claim7, wherein R has following structure of


10. The polyphenolic selenium compound having a functional group ofalkali metal ion and selenium coordination complex, as recited in claim7, wherein R has following structure of


11. The polyphenolic selenium compound having a functional group ofalkali metal ion and selenium coordination complex, as recited in claim7, wherein R has following structure of


12. The polyphenolic selenium compound having a functional group ofalkali metal ion and selenium coordination complex, as recited in claim7, wherein R has following structure of

wherein M is alkali metal ion, X is N, S or P.
 13. The polyphenolicselenium compound having a functional group of alkali metal ion andselenium coordination complex, as recited in claim 1, wherein amolecular weight thereof is 100˜600.
 14. A method for treating hepatitisB in a mammal comprising applying a therapeutically effective amount ofthe polyphenolic selenium compound having a functional group of alkalimetal ion and selenium coordination complex as recited in claim 1, or amedicinally acceptable salt thereof to the mammal.